My SARD dog recently had an ACTH test done. His cortisol levels were normal, but he has all the symptoms of elevated cortisol—he’s overweight, panting, and depressed. What’s going on?

When adrenal glands become exhausted they increase production of adrenal estrogen. This is an overwhelming pattern in SARD dogs. 90%-98% of dogs tested have elevated estrogen and/or other sex-hormones — in other words they have adrenal exhaustion.

Adrenal estrogen is unrelated to ovarian estrogen and occurs in males, females, altered and intact. Estrogen is molecularly very similar to cortisol and is documented to cause many of the same symptoms: fatigue, confusion, depression, seizures, incontinence, elevated liver enzymes, etc.

A dog in adrenal exhaustion can have a “normal” ACTH test because even though production of cortisol is on the decline, the adrenal glands can still rise to the challenge of a large stressor such as an injection of ACTH (ie. the ACTH test). It would be like falling into bed at night after a long, exhausting week at work. If you woke at 2am to find a bear in your bedroom, you could still rise to the challenge and get out. The ACTH injection is similarly the same type of stressor.

When the dog appears to have the symptoms of excess cortisol along with a normal ACTH test he may receive a diagnosis of atypical Cushing’s. This is another phrase used to describe adrenal exhaustion and in these cases it is really the rising levels of adrenal estrogen and other sex hormones that produce these symptoms.

Returning sex-hormone levels to normal will resolve many/most of these symptoms. Treatment includes cortisol and thyroid hormone replacement and minimizing environmental factors that stimulate (and exhaust) the adrenal glands.

Individual dogs react differently. Some percentage of SARD dogs clearly develop adrenal exhaustion (elevated sex-hormones) based on their blood work and clinical signs/symptoms. A small percentage of SARDS dogs go on to develop true Cushing’s disease (a tumor on either the pituitary or adrenal glands). The remaining portion of SARD dogs may tolerate slightly elevated estrogen for a few years, giving the impression that they have adapted.

Emerging evidence suggests that SARD dogs have been producing high-normal or slightly elevated levels of estrogen for some time before the onset of blindness. Then a triggering factor increases estrogen production. Examples include: springtime or autumn when adrenal activity normally ramps up, a stressful event like home remodeling or kenneling, or excessive vaccination. The tired adrenal glands are forced to secrete even more estrogen. Consequently, dogs may start having accidents in the house, an annual springtime ear infection, a seizure, or the onset of SARD.

When the demand on the adrenal gland wanes (springtime passes into summer, the dog returns from the boarding kennel, or he recovers from the stimulus of a vaccine) the estrogen level ay drop slightly to where some dogs can tolerate it again. This is a time when owners feel the dog has “adapted” and the problems are over. But “tolerate” does not mean “thrive.” Prolonged exposure to estrogen causes silent damage to internal organs such as the kidneys, liver, and brain. So testing for adrenal exhaustion is beneficial for all SARD dogs.

Yes, most definitely. Insufficient cortisol production (adrenal exhaustion) and the resulting estrogen production can contribute to a poor quality of life and gradual damage to the liver, kidney, and many other internal organs and tissues. Prompt, aggressive treatment of adrenal exhaustion may play a role in sparing some retinal cells from destruction and restoring some functional vision.

Treating adrenal exhaustion can drastically improve lethargy, confusion, depression, immune system problems, etc. Many of the owners I talk to say they “can handle the blindness” but wish they could just “have their dog back,” meaning they just want to see his normal personality return. Please see: Health Problems in an Untreated SARD Dog

Why are replacement hormones given to SARD dogs every day instead of every-other-day like some other dogs get?

In a healthy dog with working adrenal glands, daily doses of steroids suppress natural cortisol production. This happens because the body recognizes that prescription hormones are circulating in the bloodstream and knows that the body doesn’t need any more from the glands. So, dogs with working adrenal glands are given hormones every-other-day to prevent the glands from shutting off.

But if a patient has adrenal exhaustion (the adrenal glands are too tired to make sufficient cortisol) replacement hormones are required every day. Adrenal activity is low so there is very little function left to suppress anyway. The vast majority of SARD dogs fall into this category.

My vet told me there was a survey that said that SARD dogs don’t develop additional medical problems. If this is true, how come my dog is so miserable?

I believe your veterinarian is referring to a paper presented at the 2005 annual Veterinary Ophthalmology meeting. The survey concluded that the majority of SARDS dogs do not develop additional medical problems.

In that paper, fifteen owners were surveyed 10-28 months after the SARDS diagnosis. Of the 15 dogs, three had been euthanized or passed away (all three were of advanced age), another one developed diabetes, and one developed seizures. So depending on how you look at it 15% of the dogs developed a serious medical problem or 33% developed a serious medical problem and/or passed away. Either way, it’s a minority (less than half).

However, there are two important things to consider about that survey
• How the dogs’ health status was evaluated
• The definition of a “medical problem”

According to the summary, the survey asked owners two questions about the dogs’ health: whether they had symptoms of polyuria/polydipsia (excessive urination and drinking) and whether any new medical problems had appeared. From what I read, there were no diagnostic tests (lab work) performed to assess the dogs’ health. It would have been very interesting if body weight (obesity), liver function, or adrenal hormones had been measured, or if the owners had been surveyed about the variety of other symptoms SARDS dogs experience. Obesity itself is considered a medical problem and it is reported to persist in most untreated SARD dogs.

In another study presented two years earlier at the ACVO meeting, 9 of 10 SARD dogs (90%) demonstrated abnormal levels of adrenal hormones. By definition, abnormal hormone levels are also a medical problem. Hormones such as adrenal estrogen are known to have gradual, long-term effects including kidney and liver damage. Without blood tests, dog owners would be unaware of such developments and would not report them when surveyed.

That said, it is probably entirely true that only a minority (fewer than half) of SARD dogs develop the more obvious health problems (severe depression, seizures, autoimmune conditions, cancer, and liver disease, for example) but if your dog is one of them, it’s a very real problem—I know. The owners of these dogs tell me time and again how frustrating it is to hear that their dog will have a “normal, healthy life” when they can clearly see he’s suffering.

Is the concept of adrenal exhaustion new? My vet had never heard of it before.

I’m not sure why medical and veterinary schools don’t cover the stress adaptation response more fully. Dr. Selye’s now-famous work has been cited in thousands of research papers. He wrote 40 books and more than 1,700 articles on stress and related illness. So impressive have his findings been that some authorities refer to him as “the Einstein of medicine.”

Limited awareness could be due, in part, to the fact that stress is basically a condition of lifestyle. Nurses focus closely on the relationship between lifestyle and health, so nursing schools focus on the stress response. Since my background is in nursing, I applied these concepts to my work with SARD dog owners. So, to answer that part of your question, the concept is not new.

Many people resist the idea that that physical irritation and lifestyle may play a role in SARDS. It’s difficult for people to accept new information that conflicts with what they already believe to be true. And some owners would rather not know about potential problems that may happen in the future. These are normal methods of coping.

My SARD dog of two years had her total estrogen level measured. It was 35.19. My vet said this is so close to normal that it’s nothing to worry about but my dog is still lethargic and depressed. Can you tell me why?

The lab you’re referring to has set the normal range for female total estrogen at 30.00-35.00 pg/mL. It is a very precise range. Blood levels even slightly above or below that normal range are meaningful.

In some cases, doctors are not used to seeing such an exact range. It’s been my experience, however, that SARD-dog owners report lethargy, confusion, panting, excessive appetite and incontinence when total estrogen seems “only slightly” elevated—in the range of 35.14 – 35.28 pg/mL. (These values refer specifically to female dogs, but a similar pattern is noted in male dogs.) Hormone therapy to replace depleted cortisol can be very helpful in such cases.

How long does it take for hormone replacement therapy to start working? What will I notice in my dog?

It varies among individuals. Improvement in mood and energy level are often noted within 2-4 weeks. Other signs of elevated sex hormones, such as obesity, heat intolerance, and coat changes, improve over 3-9 months. Remember, it took years of chronic irritation/physical stress to reach the point of adrenal fatigue, and it takes some time to reverse that situation.

One variable that slows progress is poor GI absorption. If the intestinal tract is inflamed (IgA levels are low) the dog will have difficulty absorbing hormone pills and other medications. Improvement will be slow.

Occasionally, levels of hormones normalize quickly, almost too quickly. The drastic change may cause a short period of incontinence and confusion. This may cause practitioners to question whether hormone replacement was appropriate. However, as hormone levels equalize, these transitory signs/symptoms resolve. A good analogy is dropping a rubber ball from a great height. It bounces up and down several times (like the hormone levels) until it comes to a resting state. Follow-up testing can confirm that you are on the right track.

If a dog has been subject to elevated estrogen levels for a long time, some symptoms may persist even with treatment. The most common are the food-seeking behaviors. I’m unclear as whether this is a learned behavior or whether the appetite center in the brain has been irreversibly damaged.

Initially it was recommended that SARD dogs have an adrenal hormone panel run once lifestyle changes had been implemented. More recently it’s become clear that SARD dogs are already in adrenal fatigue within a week or two of blindness. So it is beneficial to test and treat SARD dogs for adrenal exhaustion at the time of diagnosis. An adrenal panel is distinctly different than typical Cushing’s tests because it measures adrenal estrogen. If estrogen levels are high, it is suggestive of adrenal exhaustion. Prompt treatment not only addresses the underlying adrenal problem but also restores some vision in more than 20% of cases.

Dogs other than SARD dogs can suffer from adrenal exhaustion, too. Dogs that will benefit from adrenal testing and treatment include those with:

Poorly-controlled Cushing’s disease or those dogs suffering from signs/symptoms of Cushing’s disease but with normal results on standard Cushing’s tests (Estrogen causes many effects similar to cortisol.)

My thesis is that SARDS is first and foremost an adrenal problem that stems from the “modern-day lifestyle,” that is — commercial pet food, annual vaccination, and chronic pesticide exposure — three modern-day elements that are physically irritating. Afterall, SARDS has only been diagnosed since the late 1970s.

Of these three, I suspect diet is probably the biggest piece because it’s something we do to the dogs twice a day every day. I do not believe it is any one thing in pet food, or any one type of vaccine, or a single chemical. They all irritate the body. Chronic irritation increases adrenal gland activity and the hormones that are produced there. (See: SARDS, diet, and lifestyle study.)

In addition, there certainly must be an indirect genetic tendency to the problem, otherwise every dog in the America, and certainly every dog at the local dog pound would have SARDS. And even though SARDS affects many breeds, it was first reported in Dachshunds and Miniature Schnauzers at higher rates. I’m aware of other incidences that suggest a vague genetic link, for example: a female Golden Retriever was diagnosed with SARDS and the pup she had two years earlier developed autoimmune Addison’s disease (destruction of the adrenal gland); and one breeder of Australian Terriers actually reported SARDS in both a stud dog and his daughter.

Whether the predisposition involves a flaw in the retinal cells, an over-activity of the adrenal gland (the body overreacts to even small stressors) or a predisposition to low Immmunulogobulin A / an irritated intestine is unclear. (See: Dietary changes in a SARD dog.)

Currently, this author is investigating methods of protecting retinal cells from damage early in the course of the disease. This approach, along with restoring normal adrenal function, has been shown to spare some retinal cells in about 20%-25% of cases.

Three weeks before my dog developed SARDS she was taken to the vet’s for her annual blood work, vaccinations, etc. and everything was fine. Three weeks later, WHAM, she was blind. Is there any connection to the vaccines she received?

It seems that dogs tested close the time of vision loss are already in adrenal fatigue, producing excess estrogen. (Readers please see: Overview of adrenal fatigue and Journey with a SARDS dog for discussions of adrenal fatigue.) Some of these individuals wear out their adrenal glands gradually over a very long time. Owners report that their dog had growing problems with allergies, GI problems, liver disease, head tics, panting, obesity, etc.

Other individuals seem to reach the critical hormone levels after a spike in adrenal activity such as you’re describing: some proverbial straw that breaks the camel’s back. These include vaccine incidents, intense psychological stressors (spending a week at a boarding kennel, home remodeling, etc.), pesticide application, or the arrival of spring (when adrenal activity normally increases). Below is a simple graphic. Dog #1 (dark line) has no identifiable trigger but gradually increases estrogen levels until they reach a critical level. Dog #2 has an identifiable trigger and a spike in adrenal estrogen activity just prior to SARDS onset. Of course it’s possible that all SARD dogs have a trigger and owners are just unaware of them. In either case, estrogen levels have likely crossed a critical threshold and damage the retina. Elevated estrogen is a known excitotoxin that damages nerve/retinal cells.

My dog had her adrenal hormones tested and both cortisol and estrogen were above normal. My vet expected it to be one OR the other, not both. What gives?

A small minority of SARD dogs produce both elevated adrenal estrogen and what appears to be elevated cortisol levels. This scenario warrants a closer look because these two things (elevated estrogen and elevated cortisol) do not occur at the same time. The current literature indicates one primary reason for adrenal estrogen to rise and that is due to insufficient cortisol production. So, if estrogen production were elevated, one would not expect to see simultaneously elevations in coritsol.

One explanation for this high cortisol/high estrogen scenario entails something called an isomer— a mirror-image molecule— of cortisol. (A good analogy for an isomer is to simply look at your hands: each has five fingers but the thumb is on the opposite side—a mirror image.) Under chronic stress, some individuals increase production of a hormone isomers and in this case it’s called “11-epi-cortisol.” This occurs when the body is trying hard (but failing) to make real cortisol. Isomer levels increase instead.

The laboratory tests currently available in medical/veterinary practice cannot differentiate between cortisol and 11-epi-cortisol. (Only a few limited research facilities can distinguish between them.) Consequently, 11-epi-cortisol levels also show up as “cortisol” on most laboratory tests.

Unfortunately, these isomer molecules are not useable by the body. They are inactive. The body still feels the effects of low cortisol even though the laboratory test may read high cortisol. Therefore, adrenal estrogen becomes the primary marker when evaluating and monitoring SARD-affected dogs. When adrenal estrogen is elevated, holistic veterinarians will still supplement glucocorticoids, even if the cortisol level is “high”, too. (See: Case Report #5) With this treatment both cortisol and estrogen levels return toward the normal range. Glucocorticoid replacement reduces chronic ACTH simulation, which in turn normalizes adrenal estrogen and 11-epi-cortisol production.

Yes. There have been several reports from veterinary ophthalmologists and general practice veterinarians. (See Case Report 2 or Daisy’s case.) Researchers at Iowa State University report similar findings.

A flatline ERG indicates a lack of retinal activity. It does not always mean the retina is irreversibly “destroyed”. One explanation for a temporary lack of ERG response involves a condition called “hyperpolarization” — a big word that means the retinal cells are over-stimulated and can’t relax — rather like having a charley-horse in your calf muscle. In the retina, hyperpolarized cells are temporarily unable to send visual information to the brain.

The retina becomes hyperpolarized when excessive calcium enters the cells—a process that occurs when estrogen levels are high. This is another reason it’s important to address underlying adrenal dysfunction in SARD-dogs. When the adrenal exhaustion is treated, it may be possible to spare some cells from destruction.

Later on, if retinal cells finally depolarize and some have been spared, a dog may demonstrate some functional vision even when the ERG is flatline. Veterinary ophthalmologists suspect that this limited vision is just insufficient to register on the ERG.

Is SARD an autoimmune or immune-mediated disease—and what’s the difference?

Technically, “immune-mediated” is a blanket term that covers three types of disease: 1) an allergic response that stems from some type of infection 2) antibodies that attack the patient’s own body—an autoimmune reaction— or 3) antibodies that develop on surface tissue in response to an outside irritant, such as “Farmer’s lung’.

From past research done on SARDS, we know several things. To date, no bacterial, viral or protozoal infection has been associated with SARDS cases. This would suggest that SARD is not an infection-induced allergic response (item 1, above). In 2006, two independent studies found no autoimmune antibody activity specific to SARDS dogs.(1,2) This would suggest that SARDS is not an autoimmune disease. Finally, the retina, located in a virtually closed system, is not in contact with outside irritants, which rules out item 3 as a cause. By these criteria SARDS doesn’t qualify as an immune-mediated disease. Consequently, I suspect there may be some controversy in the veterinary community when SARDS is compared to immune-mediated retinopathy in humans.

Why then, would immunoglobulin injections help some SARDS dogs? Well, research also tells us that immunoglobulins influence a vast number of functions in the body and one of those is to regulate how much calcium enters certain cells. When estrogen levels are elevated, excess calcium flows into nerve and retinal cells. Excess calcium damages the tiny organs inside the cells and the body eventually destroys these cells. Excess estrogen also suppresses immunoglobulin levels (see: retrospective study). So, by restoring normal immunoglobulin levels it may be possible to reduce calcium overload in retinal cells. This in turn, would reduce the resulting cellular damage.

1. Gilmour MA et al. Evaluation of a comparative pathogenesis between cancer-associated retinopathy in humans and sudden acquired retinal degeneration syndrome in dogs via diagnostic imaging and western blot analysis. American Journal of Veterinary Research 2006;67:877-881